Significance Of the estimated 13 million people worldwide infected with HIV-1, one million are infants and children. It has also been estimated that by the year 2000 the cumulative number of HIV-infected adults and children will rise to 30-40 million, with deaths of more than 2.5 million children throughout the world. For infants, there continues to be a lag in the use of new treatments providing less therapeutic options. Because infants have potential markers of efficacy that are unique and can be used to very quickly evaluate the usefulness of new therapies, they are the best group to target for the development of novel therapies. Objectives 9-[2-(R)-(phosphonomethoxy)propyl]adenine (PMPA) has been shown to significantly inhibit viral reverse transcription and sustain low virus loads in SIV-infected rhesus monkeys, although bone-related toxicity has been shown to occur in 25% of infants at high doses. The objective of this study was to assess whether lower doses of PMPA (10 mg/kg/day versus 30 mg/kg/day) could maintain low viral loads and health in SIV-infected infants without evidence of bone-related toxicity. Results Studies with SIV-infected animals administered PMPA at 10 mg/kg/day (prenatally via the dam and postnatally) have indicated that infants survived for extended periods and remained healthy with no evidence of toxicity. Although fetuses and infants remained healthy and free of disease with PMPA treatment at this dose, virus was still detectable in the peripheral circulation. The results of these studies emphasize the importance of this model in studying the safety and efficacy of new approaches for treating HIV-infected children. Future Directions Despite some success with new combination chemotherapies (HAART), alternative strategies are urgently needed. Thus, we will use PMPA to control viral load and illness in SIV-infected infant monkeys in order to assess the efficacy of new treatment modalities such as gene transfer. KEY WORDS pregnancy, growth, fetus, infant, PMPA, SIV, bone toxicity FUNDING NIH Grant AI3229